Evaluation of Dexamethasone-Eluting Cell-Seeded Constructs in a Preclinical Canine Model of Cartilage Repair.

IF 3.5 3区 医学 Q3 CELL & TISSUE ENGINEERING Tissue Engineering Part A Pub Date : 2025-02-01 Epub Date: 2024-11-28 DOI:10.1089/ten.tea.2024.0244
Andy J Lee, Lianna R Gangi, Yizhong Jenny Hu, Andreea T Dinescu, X Edward Guo, Chantelle C Bozynski, Keiichi Kuroki, Aaron M Stoker, Kacey G Marra, Gerard A Ateshian, James L Cook, Clark T Hung
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Abstract

In this 12-month long, preclinical large animal study using a canine model, we report that engineered osteochondral grafts (comprised of allogeneic chondrocyte-seeded hydrogels with the capacity for sustained release of the corticosteroid dexamethasone [DEX], cultured to functional mechanical properties, and incorporated over porous titanium bases), can successfully repair damaged cartilage. DEX release from within engineered cartilage was hypothesized to improve initial cartilage repair by modulating the local inflammatory environment, which was also associated with suppressed degenerative changes exhibited by menisci and synovium. We note that not all histological and clinical outcomes at an intermediary time point of three months paralleled 12-month outcomes, which emphasizes the importance of in vivo studies in valid preclinical models that incorporate clinically relevant follow-up durations. Together, our study demonstrates that engineered cartilage fabricated under the conditions reported herein can repair full-thickness cartilage defects and promote synovial joint health and function.

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在临床前犬科软骨修复模型中评估地塞米松洗脱细胞种子构建物
在这项长达 12 个月的临床前大型动物研究中,我们使用犬模型报告了工程骨软骨移植物(由异体软骨细胞播种的水凝胶组成,具有持续释放皮质类固醇地塞米松 [DEX] 的能力,培养后具有功能性机械性能,并与多孔钛基底结合)可以成功修复受损软骨。据推测,从工程软骨中释放地塞米松可通过调节局部炎症环境改善软骨的初期修复,这也与半月板和滑膜的退行性变化受到抑制有关。我们注意到,在三个月的中间时间点,并非所有组织学和临床结果都与 12 个月的结果一致,这就强调了在有效的临床前模型中进行体内研究的重要性,这些研究应包含临床相关的随访时间。总之,我们的研究表明,在本文报告的条件下制造的工程软骨可以修复全厚软骨缺损,促进滑膜关节的健康和功能。
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来源期刊
Tissue Engineering Part A
Tissue Engineering Part A Chemical Engineering-Bioengineering
CiteScore
9.20
自引率
2.40%
发文量
163
审稿时长
3 months
期刊介绍: Tissue Engineering is the preeminent, biomedical journal advancing the field with cutting-edge research and applications that repair or regenerate portions or whole tissues. This multidisciplinary journal brings together the principles of engineering and life sciences in the creation of artificial tissues and regenerative medicine. Tissue Engineering is divided into three parts, providing a central forum for groundbreaking scientific research and developments of clinical applications from leading experts in the field that will enable the functional replacement of tissues.
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